Collagen plays a key role in a number of tissues that exhibit adverse physiological changes with time. Only by documenting the biochemical parameters of collagen that are affected, can reasonable approaches be attempted to determine the cellular mechanisms operating in senescence, This program will investigate changes occurring in collagen in selected animal tissues as a function of age. The proposed investigation will survey the composition of distinct collagen types in cardiovascular, pulmonary, cartilaginous and key supportive tissues. Post-translational modifications in the long-lived collagen molecule will be delineated, in particular the quantity, nature and sites of intermolecular crosslinks. These studies will be augmented by histological identification of collagen in the tissues. In addition, recently discovered unique collagen types, associated with basement membrane structures, will be purified and their histological and biochemical fate as a function of age will be determined. Finally, the capacity to respond to external stimuli will be studied in a model system where collagen biosynthesis is under direct hormonal control.